Neuroscience letters
-
Neuroscience letters · Sep 2009
Spinal ceramide and neuronal apoptosis in morphine antinociceptive tolerance.
Opiates, like morphine, are the most effective analgesics for treating acute and chronic severe pain, but their use is limited by the development of analgesic tolerance and hypersensitivity to innocuous and noxious stimuli. Because opioids are a mainstay of pain management, restoring their efficacy has great clinical importance. ⋯ Inhibition of ceramide biosynthesis attenuated both the increase in neuronal apoptosis and the development of antinociceptive tolerance. These findings indicate that spinal ceramide upregulation is a key pro-apoptotic event that occurs upstream of the development of morphine antinociceptive tolerance and support the rationale for development of inhibitors of ceramide biosynthesis as adjuncts to opiates for the management of chronic pain.
-
Neuroscience letters · Sep 2009
Mustard oil enhances spinal neuronal responses to noxious heat but not cooling.
The TRPA1 agonist mustard oil (allyl isothiocyanate=AITC) induces heat hyperalgesia and mechanical allodynia in human skin and sensitizes rat spinal wide dynamic range (WDR) neuronal responses to noxious skin heating. We presently used electrophysiological methods to investigate if AITC affects the responsiveness of individual spinal WDR neurons to intense skin cooling. ⋯ Vehicle (mineral oil) had no effect on thermal responses. The data confirm a role for the TRPA1 agonist AITC in enhancing heat nociception without significantly affecting cold sensitivity.
-
Neuroscience letters · Sep 2009
Neuroprotective effects of group II metabotropic glutamate receptor agonist DCG-IV on hippocampal neurons in transient forebrain ischemia.
Activation of group II metabotropic glutamate receptor (mGluR) inhibits the excessive release of glutamate that may be crucial in the pathogenesis of cerebral ischemia. This study investigated the protective effects of the group II mGluR agonist (2S,2'R,3'R)-2-(2',3'-dicarboxycyclopropyl)glycine (DCG-IV), against cerebral ischemia by examining extracellular glutamate concentration ([Glu]e) and neuronal damage in a rat model of transient forebrain ischemia. Cerebral ischemia was induced by 5 min of bilateral carotid artery occlusion and hypotension. ⋯ The intraventricular injection of DCG-IV (250 pmol) significantly attenuated the [Glu]e increase and significantly increased the survival rate of CA1 neurons. Co-injection of LY341495 reversed the protective effects of DCG-IV. These results suggest that pretreatment with DCG-IV has neuroprotective effects against ischemic neuronal injuries through the inhibition of the glutamate release via the activation of group II mGluR.
-
Neuroscience letters · Sep 2009
Evidences of cannabinoids-induced modulation of paroxysmal events in an experimental model of partial epilepsy in the rat.
The anticonvulsant effect of cannabinoids (CB) has been shown to be mediated by the activation of the CB(1) receptor. This study evaluates the anticonvulsant activity of (R)-(+)-[2,3-dihydro-5-methyl-3-(4-morpholinylmethyl) pyrrolo[1,2,3-de]-1,4-benzoxazin-6-Yl]-1-naphthalenylmethanone (WIN55,212-2, CB agonist) alone or preceded by the administration of N-(piperidin-1-yl)-5-(4-iodophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide (AM251, selective CB(1) antagonist) in an experimental in vivo model of complex partial seizures (maximal dentate gyrus activation - MDA) in the rat. ⋯ Our data suggest the involvement of the CB system in the inhibitory control of hyperexcitability phenomena in a model of acute partial epilepsy. Although the MDA model per se does not induce a basal activation of CB(1) receptors, as suggested by the lack of efficacy of AM251 when administered alone, the partial suppression of WIN55,212-2-induced effects in rats pre-treated with AM251 allows to hypothesise that the WIN55,212-2-induced antiepileptic effect is strictly linked to an increased CB(1) receptor activation or to the involvement of further receptor subtypes.
-
Neuroscience letters · Sep 2009
Lactation is a natural model of hippocampus neuroprotection against excitotoxicity.
Lactation is a temporary but complex physiological condition in which hormones and neurogenic stimulation from suckling cause maternal brain plasticity. It has been shown that lactation prevents cell damage induced by excitotoxicity in the dorsal hippocampus of the dam after peripheral administration of kainic acid (KA). The aim of this study was to determine whether lactation protects the maternal hippocampus against damage induced by intracerebral application (ICV) of KA and if lactation decreases, or only delays, this damaging effect of KA. ⋯ Lactation prevented cell damage of the pyramidal layers of the hippocampus (CA1, CA3, and CA4), as compared to virgin rats. The longer period of KA exposure increased the difference in cell damage between these two conditions. The present results confirm that lactation is a natural model for neuroprotection, since it effectively prevents acute and chronic cell damage of the hippocampus induced by exposure to KA.